The HLA-A, HLA-B, and HLA-C loci and their corresponding molecular products have turned out to be highly polymorphic and functionally complex. Class I molecules not only serve as peptide receptors, but also interact with 2-microglobulin, an ` T cell receptor, CD8 and NK inhibitory molecules, all at different sites. The fact that more than 300 class I alleles have now been defined prompted us to ask the question of where polymorhpism really occurs in a class I molecule. We have used a database of 272 HLA-A, HLA-B and HLA-C alleles to illustrate how extensive the polymorphism is. Comparison of alleles and allele families have been carried out for the facilitation of studies of class I structure and function. This study is now complete.